Rat pancreatic islet perifusion techniques are utilized in conjunction with energy dispersive x-ray analyses (EDXA) of single beta and alpha cells at different moments of the acute and second phases of hormonal secretion. EDXA-measured fluctuations of calcium, phosphorus, sodium, potassium and chlorine are correlated with a) hormonal secretory rates in response to specific secretagogues and inhibitors and b) ultrastructural changes of the same islet tissue as viewed under high voltage electron microscopy and quantitated by computerized reconstruction of serially cut cells. These studies examine how specific stimulants and inhibitors influence accumulation of intracellular calcium, a pre-requisite for stimulus-secretion coupling in islet cell and determine to what extent exocytosis of secretory granules is the only means of hormonal secretion. Definition of these mechanisms can be applied to similar studies of diabetic animal models with defective islet secretory events, and ultimately provide new, basic information about the nature of diabetes mellitus at the islet tissue level.